The effect of testosterone on the gut microbiome

Introduction: The microbiota influences metabolism, immunity and even behavior, but the mechanisms by which bacteria affect specific host characteristics remain unknown. One important but understudied mechanism is the role of hormones in gut-brain crosstalk. Although the precise pathways of microbiota-hormonal signaling have not yet been deciphered, specific changes in hormonal levels correlate with the presence of the gut microbiota. The microbiota produces and secretes hormones, responds to host hormones and regulates expression levels of host hormones. An interesting but unstudied area in microbial endocrinology is the interplay between the gut microbiome and sex hormones. The aim of this study is to investigate the effect of testosterone and sex on the mouse gut microbiome. Methods: We used an in vitro experiment to test the direct effect of testosterone on bacteria in fecal samples collected from male and female mice before and after puberty. Sex specific microbiota and metabolomic differences surrounding puberty, regardless of the testosterone supplementation, were also examined. We then examined the effect of testosterone exposure in vivo, characterizing microbiota and metabolites of both male and female mice. Results: Sex specific differences were detected in the microbiota and its metabolites of mice post-puberty, but our in vitro experiment revealed that testosterone only affected the microbiota of fecal samples collected before puberty. Testosterone supplementation in vivo affected the gut microbiome and the metabolites in both male and female mice. Conclusion: Since the change in vitro was only in the prepubertal group, that wasn’t exposed to high testosterone levels before the experiment, we conclude that the shift in the microbiome after puberty is at least partially caused by the higher levels of sex hormones, mainly testosterone.